Nanoparticles find utility in numerous fields such as in nanotechnology, coatings, controlled release systems and so forth. Although various manufacturing processes have been developed to prepare polymeric nanoparticles, such processes continue to have problems, due in part to the small size of the nanoparticles, which typically have a diameter less than 20 nanometers (“nm”). There is a renewed interest in nanoparticles and in their manufacture due to the realization that functionalized nanoparticles can be considered as building blocks for a variety of nanotechnological applications, ranging from vectors for drug and DNA delivery systems to templating agents for nanoporous microelectronic materials.
The manufacturing approaches to nanoparticles can be broadly classified into two main areas, a top-down approach and a bottom-up technique. The top-down approach involves emulsion polymerization techniques, which are useful for manufacturing nanoparticles that are greater than 100 nm in diameter. Such emulsion techniques have been further refined and optimized leading to the development of microemulsion techniques that permit particles in the 20-50 nm range to be prepared.
Bottom-up techniques rely on the synthesis of discrete spherical macromolecules such as dendrimers (1-10 nm) (Fréchet et al., U.S. Pat. No. 5,514,764; Fréchet et al. U.S. Pat. No. 5,041,516) or the self-assembly of linear block copolymers into spherical structures followed by chemical crosslinking to give the final nanoparticle with dimensions from 10-50 nm (Wooley, Journal of Polymer Science Part A: Polymer Chemistry 38(9):1397-1407 (2000)).
An alternate approach to manufacturing well-defined nanoparticles has recently been developed which involves the attempted collapse and intra-molecular crosslinking of single polymer chains to give discrete nanoparticles (Mecerreyes et al., Advanced Materials 13(3):204-208 (2001)). While promising, this strategy suffers from numerous drawbacks, for example the competing inter-molecular crosslinking reaction necessitates the use of ultra-dilute reaction conditions, which precludes the viable large scale synthesis of these nanoparticles. In addition, even at these ultra-dilute conditions inter-molecular crosslinking is still evident and so the ultimate objective of collapsing a single linear chain to give a single nanoparticle is not realized.
Therefore there remains a continuing need to find improved methods of manufacturing nanoparticles. The present invention addresses those needs by means of a pseudo high dilution process that allows for the synthesis of discrete, well-defined and functionalized nanoparticles by intra-molecular crosslinking.